Signalling in T-lymphocyte development: integration of signalling pathways is the key.

alpha beta T-cell development is restricted to the thymus. Interactions between developing lymphocytes and the thymic stroma, together with bone-marrow-derived monocytes and dendritic cells, are critical for proper development of the T-cell lineage. The developmental sequence through which T-cell progenitors pass on their way to maturity is well established, and can be followed by the sequential acquisition and/or removal of cell surface molecules. Using the combination of modern genetic manipulations, such as transgenesis, gene ablation (knockouts) and targeted mutagenesis (knock-ins), with the ever-improving conditional and inducible manipulation of gene expression, we are beginning to gain an understanding of how intercellular interactions can be relayed via intracellular signalling cascades to bring about nuclear re-organisation and the differentiated mature CD4(+) and CD8(+) subpopulations.